The objective of the proposed research is to evaluate the hormonal -receptor interactions controlling hepatic bile flow. Utilization of kinetic analysis of dose-response data allows us to determine the affinity of various gastrointestinal hormones for the receptor sites and the effectiveness of the hormone in producing a response. Similar analysis allows us to determine what the specificity of the receptor is for the various hormones and what fragment of the hormone produces affinity and effectiveness. Previous studies have demonstrated that the structurally similar peptide hormones, secretin and glucagon, are both potent choleretics, but they do not utilize the same receptor site to stimulate hepatic bile flow. Glucagon potentiates secretin-stimulated bile flow and alters secretin-stimulated bile flow by non-competitive mechanisms. Evaluation of the active carboxyl-terminal fragments of gastrin and cholecystokinin (CCK) demonstrated that choleretic activity is dependent on the sulfation of the peptide fragment of CCK in position 7 to produce combination o the peptide with the receptor (affinity). The receptor, structurally, does not accommodate the non-sulfated peptide. Further endeavors will be directed toward delineating the choleretic properties of gastrin and the importance of sulfatation of this peptide in stimulating hepatic bile flow. The results of these studies will contribute to our understanding of hormonal mechanisms controlling hepatic bile production. BIBLIOGRAPHIC REFERENCES: Kaminski, D.L., Ruwart, M.J., and Willman, V.L. The Effect of Glucagon on Secretin-stimulated Bile Flow. Fed. Proc. 34:394, 1975 (Abstract). Presented FASEB, Atlantic City, N.J. 4-15-75. Ruwart, M.J., Kaminski, D.L., and Jellinek, M. Evaluation of Perfused Liver Viability. Fed. Proc. 34:395, 1975 (Abstract). Presented FASEB, Atlantic City, N.J. 4-15-75.